Method of separating acids from chemical reaction mixtures by means of apolar amines

ABSTRACT

A process for the removal of acids from reaction mixtures, comprising at least one product of value which is sparingly soluble in water, by at least one unpolar amine as an auxiliary base, which includes: a) reacting the auxiliary base with the acid with formation of a salt; b) reacting the salt formed in step a) with a further base which accepts the acid with liberation of the auxiliary base and combines with the acid to be accepted from the auxiliary base to form a salt which is very readily soluble in water; c) extraction of the mixture obtained in step b) with water or an aqueous medium, wherein the salt of the further base dissolves in the aqueous phase and the product of value, or the solution of the product of value, in a suitable solvent and the auxiliary base form at least one separate nonaqueous phase; and d) removal by distillation of at least part of any solvent present from the at least one nonaqueous phase obtained in step c), to form two nonmiscible liquid phases.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of Ser. No. 12/092,392, filed May 1,2008, which is incorporated by reference. Application Ser. No.12/092,392 is a national stage application (under 35 U.S.C. §371) ofPCT/EP2006/66397, filed Sep. 15, 2006, which claims benefit of Germanapplication 10 2005 053 540.2, filed Nov. 8, 2006. Both of which areincorporated herein by reference in their entirety.

DESCRIPTION

The present invention relates to a process for the improved removal ofacids from polar reaction mixtures by means of unpolar amines.Furthermore, the invention relates to a process for the preparation ofthiophosphoric triamides, to the thiophosphoric triamides obtainable bythis process, and to the use of these thiophosphoric triamides asadditive to urea-comprising mineral and/or organic-mineral fertilizers.

The skilled worker is frequently faced with the problem of scavengingacids liberated during a chemical reaction or removing acids fromreaction mixtures. Examples of reactions in which acids are liberated inthe course of the reaction are the silylation of alcohols or amines withhalosilanes, the phosphorylation of amines or alcohols with phosphorushalides, the formation of sulfonic esters or sulfonic amides fromalcohols or amines and sulfonyl chlorides or sulfonic anhydrides, andthe formation of acyl compounds from acid halides or anhydrides andalcohols or amines.

Usually, it is necessary to bind these liberated acids with a base, withsalt formation, in order to prevent secondary and subsequent reactionsof the product of value or simply to remove the acid from the desiredreaction product.

A process for removing acids from chemical reaction mixtures isdescribed in WO 03/062171. This process of removing acids with the aidof ionic liquids allow typically unpolar products of value to beseparated from acids in chemical reaction mixtures. A phase separationbetween the unpolar product of value and a polar ionic liquid, resultingfrom acid and added base, is exploited for this purpose. However, if theproduct of value is too polar in character, the phase separation betweenproduct of value and ionic liquid is hampered or made impossible. Polarproducts of value cannot be isolated by the strategy described in WO03/062171.

It was an object of the present invention to identify a process for theremoval of acids from chemical reaction mixtures with products of valuewhich are sparingly soluble in water, allowing a technically simpleliquid-liquid phase separation.

This object was achieved in accordance with the invention by employingan auxiliary base which is an unpolar amine for removing the acid.

The invention relates to a process for the removal of acids fromreaction mixtures, comprising at least one product of value which issparingly soluble in water, by means of at least one unpolar amine asauxiliary base, comprising the following steps:

-   -   a) reacting the auxiliary base with the acid with formation of a        salt;    -   b) reacting the salt formed in step a) with a further base,        which accepts the acid with liberation of the auxiliary base;    -   c) extraction of the mixture obtained in step b) with water or        an aqueous medium, where the salt of the further base dissolves        in the aqueous phase and the product of value, or the solution        of the product of value, in a suitable solvent and the auxiliary        base form at least one separate nonaqueous phase; and    -   d) removal by distillation of the auxiliary base and/or at least        part of the solvent which is optionally present from the at        least one nonaqueous phase obtained in step c), it being        possible for two nonmiscible liquid phases to form.

The invention furthermore relates to a process for the preparation ofthiophosphoric triamides by reacting thiophosphoryl chloride with atleast one primary or secondary amine in an inert solvent with the aid ofat least one unpolar amine as auxiliary base, proceeding in accordancewith the process according to the invention for the removal of acidsfrom reaction mixtures, to the thiophosphoric triamides obtainable usingthis process and to the use of these thiophosphoric triamides asaddition to urea-comprising mineral and/or organic/mineral fertilizers.

Phase separation in mixtures of liquids always occurs when twocomponents of the mixture differ sufficiently with regard to theirpolarity, i.e. when one component is relatively polar, while the othercomponent is relatively unpolar. A quantitative measure for assessingthe systems in which this requirement is met is the respective activitycoefficients of the one component in infinite dilution γ°° in therespective other component. As described in the literature (H. R. Null“Phase Equilibrium in Process Design”, Wiley Interscience, 1970), phaseseparation can only occur when γ°°>7.39. All systems in which the aboverequirement is met should therefore permit phase separation and shouldthus be suitable for the claimed process.

As the result of the preferably anhydrous reaction of the startingmaterials, which are susceptible to hydrolyses, in the presence of theauxiliary base (base 1) and, if appropriate, in the presence of asolvent, the present invention gives a homogeneous or heterogeneousmixture of product of value and salt of base 1 and of the acid which hasbeen formed or which is present (base 1•acid). The auxiliary base may becomprised in the reaction mixture or may be added later. The auxiliarybase itself is advantageously liquid at temperatures at which theproduct of value does not undergo significant decomposition.

To separate this mixture, a further base (base 2) is added, whichaccepts the acid. This, in turn, liberates the unpolar base 1. Moreover,the added base 2 can engage in the formation, or further transformation,of the product of value, for example by the base undergoing anucleophilic reaction (for example with ammonia, formation of phosphoricamides from phosphorus halides).

Bases which are suitable as base 2 are, in particular, those which arestronger than the base 1 used as auxiliary base. However, those whichare likewise suitable as base 2 are those bases which, on the basis ofthe pK value, are formally weaker bases than the auxiliary baseemployed, when the proton transfer is influenced by secondary effects,such as the precipitation of a salt in anhydrous systems. Here, theproton transfer is driven by the salt's lattice energy which is releasedchloride, as the driving force for completion. This is the case forexample when ammonia is used as base 2, with formation of solid ammoniumchloride, since ammonia, with a pK_(B) value of 4.77, is a weaker basethan, for example, triethylamine (pK_(B)=3.25). In any case, base 2must, together with the acid to be accepted from base 1, form a saltwhich is very readily soluble in water.

In a preferred embodiment, the nonaqueous mixture obtained in step c) ofthe process according to the invention, of product of value andauxiliary base (base 1), together with the solvent which is optionallypresent, forms a homogeneous phase. This is the case for example whenproduct of value and auxiliary base are miscible with one another (case1). In this case, the product of value is isolated by removing bydistillation all of the auxiliary base and of the solvent which isoptionally present.

However, in the presence of a suitable solvent, a homogeneous nonaqueousphase may form in step c) of the process according to the invention evenwhen product of value and auxiliary base are not miscible with oneanother (case 2). In this case, the product of value can be isolated byremoving by distillation some or all of the solvent, which results intwo liquid phases which can be separated and of which one comprises theproduct of value, while the other comprises the auxiliary base. As analternative, the auxiliary base may, again, be removed by distillationtogether with the solvent, with the product of value remaining as theresidue.

In a further preferred embodiment, the nonaqueous mixture obtained instep c) of the process according to the invention, of product of valueand auxiliary base (base 1) together with the solvent which isoptionally present, is in biphasic form (case 3). This is the case forexample when both the product of value and the solvent used arerelatively polar so that they do not mix with the unpolar amine which isused in accordance with the invention as the auxiliary base. Here,product of value and auxiliary base can be separated immediately byphase separation; if required, the solvent which is optionally presentmay subsequently be removed by distillation from the product of value.As an alternative, the auxiliary base may, again, be removed bydistillation together with the solvent, with the product of valueremaining as the residue.

In step c) of the process according to the invention, the reactionmixture is extracted with water or an aqueous medium, so that the saltof the further base (base 2•acid), which is readily soluble in water,dissolves. Since the auxiliary base is unpolar in accordance with theinvention, and the product of value too is only sparingly soluble inwater, the aqueous solution of the salt of the further base (base2•acid) forms a separate phase which can be removed readily. Ifrequired, an inert salt, for example an alkali metal halide or alkalimetal sulfate, preferably sodium chloride, may be added to the water oraqueous medium used for the extraction in order to improve phaseseparation. The product of value is stable to hydrolysis under theconditions.

The solubility of the product of value in aqueous solution of base2•acid is advantageously less than 10% by weight, preferably less than2% by weight and very especially preferably less than 0.5% by weight.

The product of value which, in case 3 described above, forms a separatephase can be separated by phase separation not only from the aqueoussalt solution, but also from base 1, which is present as a furtherseparate phase. If, in case 2 described above, the product of valueexists in the presence of a solvent, phase separation between theproduct of value and base 1 only takes place after removal of at leastpart of the volatile solvent.

Base 1 is removed and advantageously recirculated into the process.

The following schemes should clarify the principal difference betweenthe processes of cases 1 and 2 described above, in comparison with case3:

Cases 1 and 2)

Case 3)

Explanations: Starting Material 1 or 2: Susceptible to Hydrolysis;

-   Base 1: unpolar amine (auxiliary base), insoluble in water, is    recirculated into the process;-   Base 1•acid: salt;-   Base 2: polar (for example NaOH or NH₃);-   Base 2•acid: salt, readily soluble in water, is dissolved.

As a rule, the product of value takes the form of polar organic orinorganic compounds, which are generated in the reactions listedhereinbelow by way of example.

The product of value can be present in solution in a suitable solvent.Suitable solvents are those which themselves do not react with thestarting materials, which have good dissolving capacity for the startingmaterials and the product of value, and are preferably polar whilesimultaneously being sparingly soluble in water. An example of asuitable solvent is ethyl acetate. However, all other known, preferablypolar, solvents which are sparingly soluble in water, such as esters andketones, are also suitable. The solubility in water of the solvent isadvantageously less than 20% by weight, preferably less than 10% byweight and most preferably less than 5% by weight.

In the removal by distillation of the solvent from the product of value,which may or may not be carried out, it is important that the boilingpoints of solvent and product of value are sufficiently different. As arule, the boiling points of product of value and solvent should differby at least 5° C., even better by at least 10° C. It is preferred thatthe solvent has a lower boiling point than the product of value.

Suitable chemical reactions which may be carried out with the processaccording to the invention are all reactions in which acids areliberated.

Examples of reactions in which the process according to the inventioncan be applied are

-   -   alkylation reactions with alkyl or aralkyl halides, such as, for        example, methyl chloride, methyl iodide, benzyl chloride,        1,2-dichloroethane or 2-chloroethanol,    -   acylation reactions, i.e. reactions of acid halides and        carboxylic anhydrides with any substrate, for example with        alcohols or amines,    -   silylation reactions, i.e. reactions with compounds which        comprise at least one silicon-halogen bond, such as, for        example, tetrachlorosilane (SiCl₄), dimethyldichlorosilane        ((H₃C)₂SiCl₂) or trimethylchlorosilane ((H₃C)₃SiCl),    -   phosphorylation and thiophosphorylation reactions, i.e.        reactions with compounds which comprise at least one        phosphorus-halogen bond, such as, for example, phosphorus        trichloride (PCl₃), phosphorus pentachloride (PCl₅), phosphoryl        chloride (POCl₃), thiophosphoryl chloride (PSCl₃), phosphonyl        bromide (POBr₃, dichlorophenylphosphine or        diphenylchiorophosphine,    -   sulfurization reactions, i.e. sulfidation, sulfuration,        sulfonation and sulfatization reactions, for example with        sulfuryl chloride (SO₂Cl₂), thionyl chloride (SOCl₂),        chlorosulfonic acid (ClSO₃H), sulfonyl halides such as        p-toluenesulfonyl chloride, methanesulfonyl chloride or        trifluoromethanesulfonyl chloride, or sulfonic anhydrides,    -   elimination reactions in which a C═C double bond is formed with        elimination of an acid, such as, for example, hydrogen chloride        (HCl), hydrogen bromide (HBr), acetic acid or p-toluenesulfonic        acid, or    -   deprotonation reactions, in which an acidic hydrogen atom is        abstracted from the auxiliary base.

Preferably among the abovementioned types of reactions arephosphorylation, thiophosphorylation, sulfurization and silylationreactions, with phosphorylation and thiophosphorylation reactions beingespecially preferred.

The acids to be removed as per the present invention can, for example,be Brönsted acids. The acids referred to as Brönsted acids are describedin Hollemann-Wiberg, Lehrbuch der Anorganischen Chemie [Textbook ofinorganic chemistry], 91^(st)-100^(th) edition, Walter de Gruyter,Berlin New York 1985, p. 235 and p. 239.

As a rule, the compounds which are converted under silylation,phosphorylation, thiophosphorylation or sulfurization are, as a rule,those which have at least one free O—H, S—H or N—H bond, if appropriateafter deprotonation by the auxiliary base.

Acids with which the bases can form salts are, for example, hydrogeniodide (HI), hydrogen fluoride (HF), hydrogen chloride (HCl), nitricacid (HNO₃), nitrose acid (HNO₂), hydrogen bromide (HBr), carbonic acid(H₂CO₃), hydrogen carbonate (HCO₃ ⁻), methylcarbonic acid (HO(CO)OCH₃),ethylcarbonic acid (HO(CO)OC₂H₅), n-butylcarbonic acid, sulfuric acid(H₂SO₄ ⁻), hydrogen sulfate (HSO₄), methylsulfuric acid (HO(SO₂)OCH₃),ethylsulfuric acid (HO(SO₂)OC₂H₅), phosphoric acid (H₃PO₄), dihydrogenphosphate (H₂PO₄ ⁻), formic acid (HCOOH), acetic acid (CH₃COOH),propionic acid, n- and isobutyric acid, pivalic acid,Para-toluenesulfonic acid, benzenesulfonic acid, benzoic acid,2,4,6-trimethylbenzoic acid, mandelic acid, methanesulfonic acid,ethanesulfonic acid or trifluoromethanesulfonic acid, with hydrogenchloride, acetic acid, p-toluenesulfonic acid, methanesulfonic acid,2,4,6-trimethylbenzoic acid and trifluoromethanesulfonic acid beingpreferred and with hydrogen chloride being especially preferred.

In accordance with the invention, the auxiliary bases employed areunpolar amines, in particular those which have no free O—H, S—H or N—Hbond. Auxiliary bases which do not participate in the reaction asreactants are preferred.

Suitable auxiliary bases are, for example, tertiary amines of theformula (I)

NR^(a)R^(b)R^(c)  (I),

are those in whichR^(a), R^(b) and R^(c) independently of one another are in each caseC₁-C₁₈-alkyl, or are a C₂-C₁₈-alkyl, C₆-C₁₂-aryl or C₅-C₁₂-cycloalkylwhich is optionally interrupted by one or more oxygen and/or sulfuratoms and/or one or more substituted or unsubstituted imino groups, orare a radical of a five- to six-membered heterocycle containing oxygen,nitrogen and/or sulfur atoms, or two thereof together form, togetherwith the nitrogen atom to which they are bonded, an unsaturated,saturated or 5- to 7-membered aromatic ring which is optionallyinterrupted by one or more oxygen and/or sulfur atoms and/or one or moresubstituted or unsubstituted imino groups, it being possible for theabovementioned radicals to be substituted in each case by still furtheraryl, alkyl, aryloxy and alkyloxy groups, halogen atoms and/or radicalsof heterocycles, and to comprise still further hetero atoms and/orfunctional groups. Here, the term aryl group represents an aromatichydrocarbon radical having 6 to 12 C atoms, alkyl group represents abranched or unbranched saturated hydrocarbon radical having 1 to 18 Catoms, aryloxy group represents a radical which is derived from anaromatic phenol having 6 to 12 C atoms, alkyloxy group represents aradical which is derived from an aliphatic monoalcohol having 1 to 18 Catoms, and halogen represents the elements fluorine, chlorine, bromineand iodine. Heterocycles are pyrrolidine, piperidine, morpholine, furan,thiophene, pyrrole, imidazole, pyrazole, oxazole, isoxazole, thiazole,isothiazole, oxadiazole, thiadiazole, triazole, quinoline, isoquinoline,pyridine, pyrimidine, pyrazine, pyridazine or s-triazine. Further heteroatoms are nitrogen, oxygen, sulfur or phosphorus, and functional groupsare carbonyl, carboxyl, ester, cyano or nitro groups.

R^(a), R^(b) and R^(c) are preferably independently of one another ineach case C₁-C₁₈-alkyl, C₆-C₁₂-aryl or C₅-C₁₂-cycloalkyl and especiallypreferably C₁-C₁₈-alkyl, it being possible for the abovementionedradicals to be substituted in each case by still further aryl, alkyl,aryloxy and/or alkyloxy groups, halogen atoms and/or radicals ofheterocycles, and to comprise still further hetero atoms and/orfunctional groups.

Preferred meanings for the radicals R^(a), R^(b) and R^(c) are methyl,ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl(n-amyl), 2-pentyl (sec-amyl), 3-pentyl, 2,2-dimethylprop-1-yl(neopentyl), n-hexyl, n-heptyl, n-octyl, isooctyl, 2-ethylhexyl,1,1-dimethylpropyl, 1,1-dimethylbutyl, benzyl, 1-phenylethyl,2-phenylethyl, α,α-dimethylbenzyl, phenyl, tolyl, xylyl, α-naphthyl,β-naphthyl, cyclopentyl or cyclohexyl.

If two of the radicals R^(a), R^(b) and R^(c) form a chain, this may be,for example, 1,4-butylene or 1,5-pentylene, where these two radicalstogether with the nitrogen atom linking them form a pyrrolidinyl orpiperidinyl radical.

Examples of the tertiary amines are trimethylamine, triethylamine,diethylmethylamine, diethyl-n-propylamine, diethyl-n-butylamine,diethyl-tert-butylamine, diethyl-n-pentylamine, diethyihexylamine,diethyloctylamine, diethyl-(2-ethylhexyl)amine, tri-n-propylamine,di-n-propylmethylamine, di-n-propylethylamine, di-n-propylbutylamine,di-n-propyl-n-pentylamine, di-n-propylhexylamine, di-n-propyloctylamine,di-n-propyl-(2-ethylhexyl)amine, diisopropylmethylamine,diisopropylethylamine, diisopropyl-n-propylamine, diisopropylbutylamine,diisopropylpentylamine, diisopropylhexylamine, diisopropyloctylamine,diisopropyl-(2-ethylhexyl)amine, tri-n-butylamine,di-n-butylmethylamine, di-n-butylethylamine, di-n-butyl-n-propylamine,di-n-butyl-n-pentylamine, di-n-butylhexylamine, di-n-butyloctylamine,di-n-butyl-(2-ethylhexyl)amine, N-methylpyrrolidine, N-ethylpyrrolidine,N-n-propylpyrrolidine, N-isopropylpyrrolidine, N-n-butylpyrrolidine,N-sec-butylpyrrolidine, N-tert-butylpyrrolidine, N-n-pentylpyrrolidine,N,N-dimethylcyclohexylamine, N,N-diethylcyclohexylamine,N,N-di-n-butylcyclohexylamine, N-methylpiperidine, N-ethylpiperidine,N-n-propylpiperidine, N-isopropylpiperidine, N-n-butylpiperidine,N-sec-butylpiperidine, N-tert-butylpiperidine, N-n-pentylpiperidine,N-methylmorpholine, N-ethylmorpholine, N-n-propylmorpholine,N-isopropylmorpholine, N-n-butylmorpholine, N-sec-butylmorpholine,N-tert-N-n-pentylmorpholine, N-benzyl-N-methylaniline,N-benzyl-N-ethylaniline, N-benzyl-N-n-propylaniline,N-benzyl-N-isopropylaniline, N-benzyl-N-n-butylaniline,N,N-dimethyl-p-toluidine, N,N-diethyl-p-toluidine,N,N-di-n-butyl-p-toluidine, dimethylbenzylamine, diethylbenzylamine,di-n-propylbenzylamine, di-n-butylbenzylamine, dimethylphenylamine,diethylphenylamine, di-n-propylphenylamine and di-n-butylphenylamine.

The auxiliary bases are preferably tertiary amines, in particulartrialkylamines.

The following are preferred: trimethylamine, triethylamine,diethylmethylamine, diethyl-n-propylamine, diethyl-n-butylamine,tri-n-propylamine, di-n-propylmethylamine, di-n-propylethylamine,tri-n-butylamine, di-n-butylmethylamine, di-n-butylethylamine.

Especially preferred tertiary amines are triethylamine,tri-n-propylamine and tri-n-butylamine.

The abovementioned auxiliary bases can be employed individually or inmixtures with one another in order to solve the problem of theinvention.

The auxiliary base is advantageously liquid at temperatures at which theproduct of value does not undergo decomposition significantly.

For the purposes of the present invention, “no significant decompositionof the product of value” means that less than 10 mol % per hour,preferably less than 5 mol %/h, especially preferably less than 2 mol%/h and very especially preferably less than 1 mol %/h of product ofvalue undergo decomposition.

As a rule, the melting points of the especially preferred auxiliarybases are less than 50° C., especially preferably less than 25° C. andvery especially preferably less than 10° C.

In the removal by distillation of the auxiliary base from the product ofvalue, which may or may not be carried out, it is important that theboiling points of auxiliary base and product of value are sufficientlydifferent. As a rule, the boiling points of product of value andauxiliary base should differ by at least 5° C., even better by at least10° C. It is preferred that the auxiliary base has a lower boiling pointthan the product of value.

According to the invention, the auxiliary bases employed are unpolar andare therefore sparingly soluble in water at room temperature with asolubility in water of less than 10% by weight, preferably less than 2%by weight and very especially preferably less than 0.5% by weight.

The auxiliary base should be chosen in such a way that it has nodecomposing effect on the product of value, either in the form of thesalt or in the form of the free base (after addition of base 2).

To accept the acid from the salt base 1•acid, a further base (base 2) isemployed in accordance with the invention.

Such bases may comprise any desired groups such as, for example, OH, NH₂or alkoxide groups. As has already been detailed further above, they maybe stronger than base 1. If, in contrast, they are weaker bases thanbase 1, such as ammonia in relation to tertiary amines, the reaction ofbase 2 with the salt of base 1 to give the salt of base 2 withliberation of base 1 must have a distinctly negative reaction enthalpy.

Examples of added further bases (base 2) are ammonia, inorganichydroxides, alkoxides, inorganic amides, inorganic carbonates, organicamidine bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and1,5-diazabicyclo[4.3.0]non-5-ene (DBN), or polar amines which arereadily soluble in water, such as, for example, oligoethylenimine(Polymin®, BASF Aktiengesellschaft).

The following are preferably employed: sodium hydroxide (NaOH),potassium hydroxide (KOH), calcium hydroxide (Ca(OH)₂), lime water,sodium carbonate (Na₂CO₃), sodium hydrocarbonate (NaHCO₃), potassiumcarbonate (K₂CO₃), ammonia (NH₃), sodium methoxide. Sodium hydroxide andammonia are especially preferably employed.

Here, it is not possible in accordance with the invention to add base 2to the reaction mixture at the beginning since base 2 would react withthe starting materials.

Water or an aqueous medium are employed for converting the salt base2•acid into an aqueous solution. The aqueous medium can be any type ofaqueous mixture in which water is present in an amount of more than 1%by weight, preferably more than 50% by weight, especially preferablymore than 90% by weight.

In a further embodiment of the invention, base 2 is already added as anaqueous solution in step b) of the process according to the invention.

The compounds employed for the process according to the invention areadvantageously employed in the following molar ratios:

The auxiliary base (base 1) is used for example in an amount of from 0.5to 3 mol equivalents, preferably 0.8 to 1.5 mol equivalents, in eachcase based on the starting material which is present in a smaller molaramount.

The auxiliary base (base 2) is used for example in an amount of from 0.5to 10 mol equivalents, preferably 1.0 to 3 mol equivalents, in each casebased on the starting material which is present in a smaller molaramount.

Water should be employed in an amount of from 50 to 5000% by weight,preferably 100 to 1000% by weight, in each case based on the salt of thefurther base.

The procedure of the reaction is not limited and can be carried outaccording to the invention with scavenging of the acids which have beenliberated or added, batchwise or continuously and in the air or under aprotective gas atmosphere.

The reaction between the starting materials in the presence of theauxiliary base usually proceeds at temperatures of from −70° C. to +150°C., preferably from −30° C. to +50° C. The reaction with the furtherbase (base 2) usually likewise proceeds at temperatures of from −70° C.to +150° C., preferably from −30° C. to +50° C. The extraction of thesalt base 2•acid with water or an aqueous medium is preferably carriedout by dissolving the salt at temperatures of from −10° C. to +100° C.,especially preferably from −5° C. to +50° C. The two separatednonaqueous liquid phases in cases 2 and 3 described above, auxiliarybase on the one hand and product of value on the other hand, are formedabove the melting point of the product of value. The temperature rangefor the phase separation is preferably between 0° C. and 150° C.,especially preferably between 15° C. and 100° C.

All process steps can be carried out under atmospheric pressure, underpressure or else under reduced pressure. In the presence of gaseousreactants or gaseous bases, the pressure is preferably less than 50 bar.

The auxiliary base which has been removed from the process can berecirculated into the process in a manner known to the skilled worker.

If required, the auxiliary base can be washed with water or aqueoussodium chloride or sodium sulfate solution and then dried, for exampleby removing any water which may be present with the aid of an azeotropicdistillation using benzene, toluene, xylene, butanol or cyclohexane.

If required, the auxiliary base can be distilled before it is reused.

The process according to the invention allows the successful removal ofacids from chemical reaction mixtures with products of value which aresparingly soluble in water. By reaction with a further base (base 2),the salt of the unpolar auxiliary base (base 1) is reacted, withliberation of the auxiliary base, to give the salt of base 2, which saltis considerably more readily soluble in water than the salt of theunpolar auxiliary base.

Since the product of value, too, is only sparingly soluble in water, thesalt of base 2 can be separated by a technically simple process of aliquid-liquid phase separation following extraction with water or anaqueous medium. The technically complicated handling of solids canthereby be dispensed with. The auxiliaries can be worked up in absenceof the product of value, so that the latter is less contaminated.

The process according to the invention can successfully be employed inall of the reactions which have been described further above, inparticular in the preparation of (thio)phosphoric acid derivatives suchas amides, esters and mixed species.

Accordingly, the invention further relates to the preparation ofthiophosphoric triamides by reacting thiophosphoryl chloride with atleast one primary or secondary amine using the process described above.

It is known that thiophosphoric triamides are hydrolyzed relativelyreadily to give the corresponding phosphoric triamides. In the presenceof moisture, thiophosphoric triamides and their corresponding phosphorictriamides are, as a rule, present as a mixture with one another. Hereinthe term “thiophosphoric triamide” therefore refers not only to the purethiophosphoric triamides, but also to their mixtures with thecorresponding phosphoric triamides.

In accordance with the invention, thiophosphoric triamides are preparedby reacting thiophosphoryl chloride with at least one primary orsecondary amine in an inert solvent with the aid of at least one unpolaramine as the auxiliary base, comprising the following steps:

-   -   a) reaction of the auxiliary base with the halogen chloride        formed during the reaction, with formation of a chloride salt;    -   b) reaction of the chloride salt formed in step a) with ammonia,        which accepts the hydrogen chloride with liberation of the        auxiliary base;    -   c) extraction, of the mixture obtained in step b) with water or        an aqueous medium, where the ammonium chloride formed dissolves        in the aqueous phase and the solution of the product of value in        the inert solvent and the auxiliary base form at least one        separate nonaqueous phase; and    -   d) removal by distillation of the auxiliary base and/or of at        least some of the inert solvent from the at least one nonaqueous        phase obtained in step c), it being possible for two nonmiscible        liquid phases to be formed.

At least one primary or secondary amine is employed for reacting thethiophosphoryl chloride.

These compounds are advantageously compounds of the general formula (II)

In this formula, R¹ and R² independently of one another are hydrogen,alkyl, alkenyl, cycloalkyl, aryl or hetaryl.

The alkyl radicals preferably have 1 to 20 C atoms, especiallypreferably 3 to 5 C atoms, the alkenyl radicals preferably have 2 to 20C atoms, especially preferably 3 to 6 C atoms, the cycloalkyl radicalspreferably have 3 to 20 C atoms, especially preferably 5 to 7 C atoms,and the aryl radicals preferably have 6 to 10 C atoms. Aryl ispreferably phenyl or naphthyl.

Hetaryl is a radical derived, for example, from furan, thiophene,pyrrole, imidazole, pyrazole, oxazole, isoxazole, thiazole, isothiazole,oxadiazole, thiadiazole, triazole, quinoline, isoquinoline, pyridine,pyrimidine, pyrazine, pyridazine or s-triazine. Especially preferredhetaryl radicals are derived from furan, thiophene and imidazole.

In an advantageous embodiment, the two radicals of the amino grouptogether form an alkylene or alkenylene chain which, together with thenitrogen atom linking them, forms a 3- to 6-membered, preferably5-membered, ring system which, if appropriate, comprises one or morefurther hetero atoms chosen from the group consisting of oxygen,nitrogen and sulfur.

The substituents R1 and R2 can additionally have attached to them one ormore radicals such as, for example, halogen, cyano, C₁- to C₆-alkylthio,C₁- to C₆-alkoxy, C₆- to C₁₂-aryl, C₁- to C₆-(di)alkylamino, toC₆-alkoxycarbonyl, aryloxycarbonyl, carbamoyl, hydroxyl, amino, sulfo ornitro. The substituents R¹ and R² especially preferably comprise halogenor amino groups.

Alkylamines are preferably employed, especially preferably n-butylamineand/or n-propylamine.

The primary or secondary amines can be used individually or as a mixturewith one another, for example a mixture of two or more alkylamines, amixture of two or more arylamines or a mixture of in each case one ormore alkylamine(s) and arylamine(s). An advantageous mixture isn-butylamine and n-propylamine with n-butylamine contents of 40 to 99%by weight. An n-butylamine content of from 60 to 80% by weight ispreferred and a content of 72 to 78% by weight is especially preferred.

The amines are preferably used in a molar ratio of from 0.9 to 1.1 molper mole of thiophosphoryl chloride, especially preferably from 0.95 to1.05 mol of amine per mole of thiophosphoryl chloride. In anadvantageous embodiment, approximately 1 mol of amine is employed permole of thiophosphoryl chloride.

In accordance with the invention, the thiophosphoryl chloride is reactedin an inert polar solvent.

Solvents which can be employed in accordance with the invention are allknown inert polar solvents. Examples of solvents which can be used are:acetone, methyl ethyl ketone, isobutyl methyl ketone, diethyl ketone,diethyl ether, di-n-butyl ether, tert-butyl methyl ether, tert-butylethyl ether, tetrahydrofuran, dioxane, acetic esters such as ethylacetate, methyl acetate, propyl acetate, butyl acetate or 2-ethylhexylacetate, dimethylformamide, dimethyl sulfoxide, acetonitrile, diethylphthalate, dioctyl adipate, chloroform, dichloromethane,methylchloroform or mixtures of these. It is preferred to employ ethylacetate.

The inert polar solvents can be employed alone or as a mixture of two ormore thereof.

The process according to the invention is preferably used for thepreparation of N-alkylthiophosphoric triamides, for exampleN-n-butylthiophosphoric triamide or N-n-propylthiophosphoric triamide.

To this end, thiophosphoryl chloride and a primary alkylamine, forexample n-butylamine, are reacted in molar ratios of preferably 0.9 to1.1 mol of amine per mole of thiophosphoryl chloride in an inertsolvent, for example ethyl acetate. The auxiliary base used is atrialkylamine, for example tri-n-butylamine, which is reacted to givethe tri-n-butylamine hydrochloride. In a second reaction step, theN-alkylthiophosphoryl dichloride which has been formed in the firstreaction is reacted with ammonia at temperatures of between preferably−20° C. and 50° C. to give the desired product N-alkylthiophosphorictriamide. In parallel with, and independently of, the second reactionstep, ammonia acts as base 2 and accepts the hydrogen chloride from thetrialkylamine hydrochloride with formation of ammonium chloride.

Ammonia is preferably used in a molar ratio of from 2 to 15 mol per moleof thiophosphoryl chloride, especially preferably 2.1 to 10 andespecially preferably 2.2 to 40 7 mol of ammonia per mole ofthiophosphoryl chloride. In an advantageous embodiment, approximately 4to 6 mol of ammonia are employed per mole of thiophosphoryl chloride.

The extraction of the reaction mixture with sufficient amounts of waterin step c) of the process according to the invention gives rise to anaqueous solution of ammonium chloride and an organic phase comprisingthe inert solvent, trialkylamine and N-alkylthiophosphoric triamide. Asa rule, the amount of water employed for the extraction is in the rangeof from approximately 10 to approximately 100 mol of water per mole ofN-alkylthiophosphoric triamide, preferably in the range of from 15 to 50mol of water per mole of N-alkylthiophosphoric triamide.

The extraction may be carried out in one or more steps and may beperformed both continuously and batchwise. It is preferred to perform amulti-step extraction, for example in a mixer-settler arrangement whichis known to the skilled worker and which consists of dispersing stepsand phase separators, or in a pulsed-stirred extraction column. Thenumber of theoretical plates should amount to 1 to 10, preferably 3 to5. To lose as little product of value as possible, it is advantageous tosubject the aqueous phase from the extraction with the solvent ethylacetate to a back extraction in the same apparatus. Some of the waterused for the extraction may advantageously be added to the reactionmixture in a separate reactor or a mixing device even before the actualextraction apparatus, in order to allow sufficient time for thedissolution of the 20 ammonium chloride in the aqueous phase.

After removal of the inert solvent by distillation, a two-phaseliquid-liquid mixture (case 2, see above) of a trialkylamine phase andan N-alkylthiophosphoric triamide phase is formed within a temperaturewindow of between 15° C. and 100° C.

As an alternative, it is also possible to evaporate almost all of thetrialkylamine together with the inert solvent, with the product of valueN-alkylthiophosphoric triamide remaining as a residue. This evaporationmay be performed for example with a thin-film evaporator, multi-phasecoiled-tube evaporator, climbing film evaporator or short pathevaporator with a short residence time, immediately after theextraction, whereby the thermal stress of the product of value is keptat a minimum. If a longer residence time is acceptable, it is alsopossible to employ falling-film evaporators or long-tube evaporators mayalso be employed. In a preferred embodiment, a two-step evaporation iscarried out in a thin-film evaporator with a total residence time inboth steps of less than 2 minutes. The pressure in the first thin-filmevaporator step is 50 to 150 mbar, preferably 60 to 90 mbar. Thetemperature in the first thin-film evaporator step is 80 to 150° C.,preferably 100 to 130° C. The pressure in the second evaporator step is0.1 to 20 mbar, preferably less than 2 mbar, and the temperature is 80to 140° C., preferably 90 to 100° C. Since the ammonium chloride hasbeen extracted previously in accordance with the invention, thisevaporation causes no precipitations or solids formation whatsoever,which would make the operation of the apparatus more difficult.

The vapors forming during evaporation may be condensed and subsequentlyprocessed in a solvent column, for example a dividing-wall column, andbe circulated into the process.

The invention furthermore relates to thiophosphoric triamides which areobtainable by the above-described process.

The thiophosphoric triamides which are obtainable by the processaccording to the invention preferably have a low residual ammoniumchloride content. In a specially preferred embodiment of the invention,the thiophosphoric triamides obtainable by the process according to theinvention have an ammonium chloride content of <500 ppm (w/w), veryespecially preferably of <100 ppm (w/w), in each case based on thethiophosphoric triamide.

In a further preferred embodiment of the invention, the thiophosphorictriamides obtainable by the process according to the invention have acombined residual content of inert solvent and auxiliary base of <1% byweight, especially preferably of <0.5% by weight, in each case based onthe thiophosphoric triamide.

Thiophosphoric triamides, specifically N-n-butylthiophosphoric triamide(NBPT) or N-n-propylthiophosphoric triamide, are potent ureaseinhibitors which are employed in urea-based fertilizer compositions.Such urease inhibitors can be used for improving the efficiency of theurea fertilization since losses as the result of the urease-catalyzeddegradation of urea in the soil are reduced. (Trenkel, M. E.,“Controlled-Release and Stabilized Fertilizers in Agriculture”, IFA1997, ISBN: 2-9506299-0-3).

The invention further relates to the use of the thiophosphoric triamideswhich have been prepared in accordance with the process according to theinvention as additive to urea-comprising mineral and/or organic/mineralfertilizers.

The invention is further illustrated by the following examples.

EXAMPLES Example 1 Preparation of N-n-Butylthiophosphoric Triamide(NBPT) in Accordance with Case 2

423.5 g (2.5 mol) of thiophosphoryl chloride and 937.5 g of ethylacetate were initially introduced. A mixture of 193.7 g (2.65 mol) ofn-butylamine, 440.2 g (2.375 mol) of tributylamine and 316.6 g of ethylacetate were added dropwise to this mixture at not more than 30° C. Thetemperature was maintained at 30° C. by cooling. This gave a clearsolution. Stirring of the mixture was continued for 3 hours at roomtemperature.

Thereafter, ammonia at 0° C. was passed in until the uptake wascomplete. The ammonia uptake amounted to 5 to 6 mol equivalents. Thisgave a fluid suspension of precipitated ammonium chloride andN-n-butylthiophosphoric triamide as product of value, dissolved in ethylacetate. The mixture was warmed to room temperature. 1406 g of waterwere added and stirring was continued at room temperature. During thisprocess, all of the ammonium chloride dissolved.

The resulting clear phases were separated, and the organic phase wasconcentrated. After most of the ethyl acetate had been removed, a topphase of tributylamine and a bottom phase of liquid NBPT were formed atapproximately 60° C. The phases were separated, and an NBPT melt wasobtained and was treated, at 50° C., with 1200 g of water with atemperature of 50° C. The mixture was cooled, with stirring, duringwhich process the NBPT separated out as a solid. The solid was removedby filtration and dried.

This gave 364.8 g of product with an NBPT content of 76% by weight(yield 66%).

Example 2 Preparation of N-n-Butylthiophosphoric Triamide (NBPT) inAccordance with Case 3

In a reaction proportioning pump, a stream of 68 mi/h thiophosphorylchloride was combined with a stream of 876 ml/h of a mixture ofn-butylamine and tri-n-butylamine (0.079:1 w/w) with a residence time of13 s, while cooling with ice-water. The discharge from the pump waspassed for 1 hour into a reactor into which tributylamine (approx. 10:1vol feed:vol Bu₃N) had been introduced, while continuously passing in anexcess of ammonia gas at 0° C. The resulting milky-white suspension wastreated with 306 g of water and heated to 40° C. A three-phase system ofaqueous bottom phase, middle phase of product of value and tributylaminephase at the top was formed.

1. (canceled)
 2. The process according to claim 7, wherein the auxiliarybase is separated off and recirculated into the process. 3-6. (canceled)7. A process for the preparation of thiophosphoric triamides by reactingthiophosphoryl chloride with at least one primary or secondary amine inan inert solvent with the aid of at least one unpolar amine as anauxiliary base, comprising the following steps: a) reacting theauxiliary base with the hydrogen chloride formed during the reaction,with formation of a chloride salt; b) reacting the chloride salt formedin step a) with ammonia, which accepts the hydrogen chloride withliberation of the auxiliary base; c) extracting the mixture obtained instep b) with water or an aqueous medium, wherein ammonium chlorideformed dissolves in the aqueous phase and the solution of the product ofvalue in the inert solvent and the auxiliary base form at least oneseparate nonaqueous phase; and d) removing by distillation of at leastsome of the inert solvent from the at least one nonaqueous phaseobtained in step c), to form two nonmiscible liquid phases. 8.(canceled)
 9. The process according to claim 7, wherein the auxiliarybase is a tertiary amine. 10-11. (canceled)
 12. The process according toclaim 7, wherein the auxiliary base is triethylamine, tri-n-propylamineor tri-n-butylamine. 13-16. (canceled)
 16. The process according toclaim 7, wherein the acid is liberated during the course of aphosphorylation or thiophosphorylation reaction. 17-20. (canceled)